Chemical ablation of recurrent and persistent secondary hyperparathyroidism after subtotal parathyroidectomy.

BACKGROUND: Despite preoperative localization or intraoperative parathyroid hormone, monitoring increased the operative successful rate, recurrent, and persistent secondary hyperparathyroidism are still unavoidable after parathyroidectomy or reoperation. We present our experience of using percutaneous ethanol injection therapy (PEIT) in treating these patients. PURPOSE: To conduct a prospective study of 49 patients with recurrent and persistent hyperparathyroidism using PEIT after subtotal parathyroidectomy or reoperative failure. PATIENTS AND METHODS: From January 2001 to August 2009, 49 patients with recurrent or persistent 2HPT after subtotal parathyroidectomy received PEIT. All dialysis patients were divided into 2 groups: recurrent group (n = 28) and persistent group (n = 21). Before PEIT, every patient received sestamibi-(99m)Tc scintigraphy (MIBI scanning), neck ultrasonography (US), bone scanning (T-score and Z-score), and parathyroid function testing. We compared the responses to PEIT treatment in the recurrent and persistent groups with the following parameters: treatment success rate, improvement in bone density, concurrence in diagnosis between US and MIBI scanning and complications. RESULTS: Treatment success was defined as intact PTH < 300 pg/mL; recurrent group is 25 of 28 (89.3%) and persistent group is 20 of 21 (95.2%) (P = 0.694). There was no difference in success rate statistically. T-score in recurrent group before PEIT was -1.2 ± 0.9 and after treatment was -0.6 ± 0.6 (P = 0.004), which is statistically significant. In the persistent group, T-score before PEIT was -1.2 ± 1.0 and after treatment was -0.8 ± 0.6 (P = 0.101). There was no significant difference. For consistence between neck US and MIBI scanning were concordant in the recurrent group in 20 of 28 (71.4%); in persistent group, it was 14 of 21 (66.6%) (P = 0.245); there was no significant difference. Regarding the complications, only hypocalcemia was significantly more common in the recurrent group. Hypocalcemia occurred in 14 of 28 patients in the recurrent group and 6 of 21 in the persistent group (P = 0.022). CONCLUSIONS: Regardless of which group patient was in, PEIT can achieve satisfying result when parathyroid masses were detected by US. Subtotal parathyroidectomy plus PEIT was probably the best combination for treatment of secondary hyperparathyroidism.

Expression of estrogen receptor-alpha and Ki67 in relation to pathological and molecular features in early-onset infiltrating ductal carcinoma.

Estrogen causes breast cancer by triggering proliferation via an estrogen receptor (ER)-mediated mechanism. However, paradoxically, ER alpha, one of the two known ER subtypes, and the proliferation marker, Ki67, are not usually expressed in the same breast tumor. To explore whether ER alpha-positive tumors and proliferating (Ki67-positive) tumors have different tumorigenic characteristics, we performed an immunohistochemical study on 74 early-onset infiltrating ductal carcinomas of the breast. To test this hypothesis, we examined whether ER alpha-positive and Ki67-positive tumors showed differences in (i) pathological grade, (ii) three indices of tumor grade (tubule formation, nuclear pleomorphism, and mitotic number), and (iii) expression of important proteins implicated in breast tumorigenesis (cyclin D1, ErbB2, ATM, BRCA1, Rb, p53, and p21). The results of the multigenic analysis showed that ER alpha and Ki67 were the only two important markers significantly and independently associated with tumor grade, consistent with the above hypothesis. ER alpha-positive, Ki67-negative tumors frequently displayed a low tumor grade (i.e. being well differentiated), whereas Ki67-positive, ER alpha-negative tumors were more likely to exhibit a high tumor grade. In addition, positive ER alpha expression (46 of 74 cases, 62%) correlated well with positive cyclin D1 expression (p < 0.005), less nuclear pleomorphism (p < 0.001), and a low mitotic count (p < 0.005), whereas positive Ki67 expression (36 of 74 cases, 49%) correlated with reduced BRCA1 expression (p < 0.01) and high mitotic activity (p < 0.01). These findings suggest that the expressions of ER alpha and Ki67 might be involved in distinct pathological and molecular features during breast cancer development.

High-resolution 19p13.2-13.3 allelotyping of breast carcinomas demonstrates frequent loss of heterozygosity.

In breast cancer, a high frequency of genomic deletion is found in chromosomal region 19p13. Of particular interest is that the LKB1 gene (also known as STK11) has been mapped to this region. LKB1 is responsible for Peutz-Jeghers syndrome (PJS), a genetic disease characterized by mucocutaneous pigmentation and gastrointestinal hematoma with an increased risk of developing cancer, including breast cancer. To further clarify the role of chromosomal region 19p13.2-13.3 in the pathogenesis of breast cancer and to identify more precisely candidate tumor-suppressor genes (TSGs) for positional cloning studies, we performed detailed high-resolution allelotyping analysis to detect allelic loss or loss of heterozygosity (LOH) in this region on microdissected samples from 140 primary breast tumors using 24 microsatellite markers. The highest frequencies of LOH were seen with D19S883 (30%) and D19S216 (29%), both at 19p13.3, D19S922 (28%), at 19p13.3-19p13.2, and D19S865 (39%), at 19p13.2; in addition, identification was made of at least four common deletion regions, including the LKB1 locus, that are centered on these four markers. In all the cases, we found discontinuous allele loss at several 19p13.2-13.3 sites in the same tumor (with the markers with the highest frequency of LOH adjacent to markers retaining heterozygosity), suggesting the presence of multiple TSGs. Interestingly, in tumors, the extent of allelic loss at these markers (measured as the fractional allele loss) increased significantly as the tumors progressed to poorer grades (P < 0.05). We conclude that 19p13.2-13.3 allele loss is a common event in the pathogenesis of breast carcinoma that often involves discontinuous LOH of multiple, localized TSGs (including LKB1), the concurrent inactivation of which may contribute to breast cancer progression.